Laboratory of Cancer Biology, College of Life Sciences, Capital Normal University, 105 Xi San Huan Road (N), Beijing, China.
Eur J Cell Biol. 2010 Jul;89(7):557-63. doi: 10.1016/j.ejcb.2010.01.004. Epub 2010 Feb 26.
Dynamic methylation/demethylation of histones and non-histone proteins occurs during the cell cycle. Lysine-specific demethylase 1 (LSD1) exhibits diverse transcriptional activities through catalyzing demethylation of mono- and di-methylated histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). We show here that inhibition of LSD1 expression by siRNA leads to abnormal chromosomal segregation in unperturbed mitosis and abnormal centrosome duplication, and is associated with decreased protein levels of MAD2 and BUBR1. LSD1 positively regulates the BUBR1 and MAD2 promoter activity and maintains local monomethylation status of H3K9, which is a repressive histone mark for gene transcription. Expression of exogenous BUBR1 and MAD2 in LSD1-depleted cells partially rescues the defect of chromosome segregation. Our results suggest that LSD1 plays a role in chromosomal segregation during mitosis partially through transcriptional regulation of BUBR1 and MAD2.
组蛋白和非组蛋白的动态甲基化/去甲基化发生在细胞周期中。赖氨酸特异性去甲基酶 1（LSD1）通过催化单甲基化和二甲基化组蛋白 H3 赖氨酸 4（H3K4）和赖氨酸 9（H3K9）的去甲基化，表现出多种转录活性。我们在这里表明，siRNA 抑制 LSD1 的表达会导致未受干扰的有丝分裂中染色体分离异常和中心体复制异常，并与 MAD2 和 BUBR1 蛋白水平降低有关。LSD1 正向调节 BUBR1 和 MAD2 启动子活性，并维持 H3K9 的局部单甲基化状态，这是基因转录的抑制性组蛋白标记。在外源表达 LSD1 耗尽细胞中的 BUBR1 和 MAD2 可部分挽救染色体分离缺陷。我们的结果表明，LSD1 在有丝分裂过程中的染色体分离中发挥作用，部分是通过对 BUBR1 和 MAD2 的转录调控。
